Several research institutions have reported biosensors that use a magnetic sensor element to indirectly detect a biomolecular using a magnetic substance as a label. Various types of magnetic sensor elements can be used for this type of detection. For example, there have been proposed a detection method using a magneto-resistance element (H. A. Ferreira, et. al, J. Appl. Phys., 93 7281 (2003)), a detection method using a Hall element (Pierre-A. Besse, et. al, Appl. Phys. Lett. 80 4199 (2002)), a detection method using a Josephson element (SeungKyun Lee. et. al, Appl. Phys. Lett. 81 3094 (2002)), a detection method using a coil (Richard Luxton, et. al, Anal. Chem. 16 1127 (2001)), and a detection method using a magneto-impedance element (Horia Chiriac, et. al, J. Magn. Magn. Mat. 293 671 (2005)). The detection methods for a biologic substance using such elements have different characteristics. In particular, the magneto-impedance element advantageously has a simple structure.
A magneto-impedance element has an elongated shape and is made of a magnetic material of uniform composition or a nonmagnetic conductor coated with a magnetic material. The magneto-impedance element is more easily magnetized in the direction perpendicular to the longitudinal direction and has a multi-domain structure when no magnetic field is applied thereto (see FIG. 7).
When a high-frequency current flows through the element, the electrons flow through the surface of the element because of the skin effect. If a magnetic field is applied to the element, the magnetic permeability of the element varies, and as a result, the impedance of the element varies depending on the applied magnetic field. That is, the magnitude of the magnetic field applied to the element can be measured by measuring the impedance of the element. However, the magneto-impedance element detects the magnetic field in the longitudinal direction thereof.
In the literature by Horia Chiriac, et al. described above, detection of a DNA using a magneto-impedance element is proposed. A magneto-impedance element is coated with a polymer, and DNA having a desired base sequence is fixed thereto by the action of biotin. The magneto-impedance element is immersed in a solution containing a magnetic substance. However, a DNA to be examined is previously fixed to the magnetic substance by the action of biotin. If the DNA to be examined, that is, the DNA fixed to the magnetic substance in this case is complementary to the DNA fixed to the surface of the magneto-impedance element, The DNAs are bonded to each other, and therefore, the magnetic substance is fixed to the surface of the magneto-impedance element. Since the magneto-impedance element exhibits an impedance depending on the stray magnetic field from the magnetic substance, whether the DNAs are complementary to each other or not can be indirectly detected.
As described in the literature by Horia Chiriac, et al. described above, the impedance is measured with an electric circuit that has a fixed resistor and an alternating-current power supply connected in series with the magneto-impedance element by measuring the voltage across the fixed resistor. The change of the impedance can be determined by comparing the impedances measured before and after the magnetic particle is fixed to the magneto-impedance element. The impedance of the magneto-impedance element after the magnetic substance is fixed thereto depends on the magnitude of the magnetic field applied by the fixed magnetic substance to the magneto-impedance element. However, quantitative measurement of the magnetic substance has been difficult because the magnetic field applied to the magneto-impedance element varies with the position at which the magnetic substance is fixed to the magneto-impedance element.
When the difference of the impedance between before and after the magnetic substance is fixed to the magneto-impedance element is measured, fixing of the target substance labeled with the magnetic particle to the element can take long. In such a case, if the measurement environment such as the element temperature differs between before and after the target substance is fixed, an impedance change independent of the magnetic particle occurs. For example, fixing of a DNA takes several hours. Therefore, the measurement environment has to be strictly controlled for the entire period from before the fixing until the fixing is completed. Therefore, in order to precisely compare the detections signals obtained at significantly different times, a special apparatus can be needed.